ArticleJournal of molecular and cellular cardiology2018
The stress kinase JNK regulates gap junction Cx43 gene expression and promotes atrial fibrillation in the aged heart.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Association BetweenFrontiers in cardiovascular medicine · 2020Pooled it
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- JNK2 Is a Stress Integrator Driving Atrial Fibrillation Pathogenesis in Aging via Gut-Heart Crosstalk.Circulation · 2026Article
- Identification and validation of five hypoxia- and immune-related hub targets in atrial fibrillation.Journal of cardiothoracic surgery · 2026Article
- Differential effects of semaglutide and colchicine on atrial remodeling in rats with reduced ejection fraction after myocardial infarction.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Mechanisms of Atrial Fibrillation in Heart Failure: Uncovering Therapeutic Targets in the Atrial Substrate.Current heart failure reports · 2026Review
- Colchicine in atrial fibrillation: mechanisms, highlights, and current evidence.Frontiers in pharmacology · 2026Review
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview.Cells · 2025Review
- The Shenlian Fumai Granule attenuates Ach-CaClFrontiers in cardiovascular medicine · 2025Article
- Atrial myocyte senescence as a driver of atrial fibrillation: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2025Review
- Alda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity.Journal of molecular and cellular cardiology · 2024Article
- Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms.Aging cell · 2024Review
- Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.The Journal of membrane biology · 2024Article
- c-Jun N-terminal kinase signaling in aging.Frontiers in aging neuroscience · 2024Review
- p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.Nature cardiovascular research · 2023Article
- Long-Term Alcohol-Activated c-Jun N-terminal Kinase Isoform 2 Preserves Cardiac Function but Drives CaCells · 2023Article
- Advances in basic and translational research in atrial fibrillation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhythmogenicity. However, direct evidence for JNK-mediated impairment of intercellular coupling (cell-cell communication) in the intact aged atrium is lacking, as is evidence for whether and how JNK suppresses Cx43 in the aged human atrium. METHODS AND
resultsJNK activity in human atrial samples is correlated with both reduced Cx43 expression and increasing age. Using a unique technique of optical mapping space constant measurement, we found that impaired intercellular coupling and reduced Cx43 were linked to enhanced activation of JNK in intact aged rabbit atria. These JNK-associated alterations were further confirmed in naturally JNK activated aged mice and in cardiac-specific inducible MKK7D (JNK upstream activator) young mice. Moreover, JNK inhibition, using either JNK specific inhibitors in aged wild-type (WT) mice and JNK activator anisomycin-treated young WT mice or JNK1/2 dominant-negative mice with genetically inhibited cardiac JNK activity, completely eliminated these functional abnormalities. Furthermore, we discovered for the first time that long-term JNK activation downregulates Cx43 expression via c-jun suppressed transcriptional activity of the Cx43 gene promoter.
conclusionOur results demonstrate that JNK is a critical regulator of Cx43 expression, and that augmented JNK activation in aged atria downregulates Cx43 to impair cell-cell communication and promote the development of AF. JNK inhibition may represent a promising therapeutic approach to prevent or treat AF in the elderly.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.